Glycine plays a major role in mammalian metabolism. It is principally oxidized by glycine decarboxylase, an extremely complex protein which contains four nonidentical subunits and requires four coenzymes for its catalytic function. There are at least five hereditary metabolic disorders which present with defective glycine metabolism. Most of these disorders have associated mental retardation. In one of these, nonketotic hyperglycinemia, glycine decarboxylase is deficient and it is proposed to be inhibited or repressed in the other disorders. We propose to study this enzyme in isolated rat liver parenchymal cells and to determine the effect of changes in culture conditions on the levels of the enzyme. Similar studies will be conducted with human skin fibroblasts. Presently, the ability of these cells to oxidize glycine is in question. In addition, we will isolate the enzyme from human placenta or liver and determine its kinetic properties and the effect of various metabolites on its kinetic properties. It is hoped that these investigations will provide the basic knowledge required in order that disorders of glycine metabolism might be effectively treated and/or prevented.